Infective endocarditis (IE) is a disease with a high degree of morbidity that can result in death. Healthcare- associated (HCA) IE is often due to non-oral staphylococcal bacteria and is associated with cardiac surgery, intravascular catheters, and cardiac devices. In contrast, community-acquired (CA) IE is typically due to streptococci in patients with pre-existing heart valve abnormalities. Prior studies provide some evidence that the periodontium and its biofilm may be a significant source of the bacteremia that results in CA-IE. However, no well-controlled studies have directly investigated the association of periodontal disease, periodontal bacteria, and CA-IE. Aim 1 of this multi-center case-control study is to determine if poor oral hygiene, gingivitis or periodontitis is associated with infective endocardits caused by any bacterial species. To address this aim, standardized measures of oral hygiene, gingivitis and periodontitis will be compared in 112 recently hospitalized patients with CA-IE (cases) and 224 healthy patients from the surrounding community who have cardiovascular risk factors for CA-IE but have not had the disease (controls). Aim 2 will determine if poor oral hygiene, gingivitis or periodontitis is associated with infective endocarditis caused by bacteria that ARE typically associated with poor oral hygiene or periodontal diseases. To address this aim, oral hygiene, gingivitis, and periodontitis will be compared among case patients with CA-IE who have positive blood cultures for oral bacteria that typically reside in the oral cavity and control patients from specific Aim 1. Aim 3 will determine if poor oral hygiene, gingivitis or periodontitis is associated with infective endocarditis caused by bacteria that ARE NOT typically associated with poor oral hygiene or periodontal disease. To address this aim, oral hygiene, gingivitis, and periodontitis will be compared among case patients with CA-IE who have positive blood cultures for non-oral bacteria and control patients from Specific Aim 1. If clinically and statistically significant associations are found between poor oral hygiene, gingivitis or periodontal disease and CA-IE, this study will transform our understanding of risk factors for CA-IE and will be a major step forward because it will provide supporting evidence that improving oral hygiene and maintaining periodontal health may reduce the risk for CA-IE. This has the potential to reduce the incidence of CA-IE and its associated morbidity, mortality, and cost. It would provide important information for future clinical guidelines for the prevention of endocarditis and be an important contribution to the public health in the U.S. and throughout the world for all people at risk for infective endocarditis.